Mutations &

Genetic
Disorders
 MUTATIONS
A mutation may be defined as a permanent change in
the DNA. Mutations that affect the germ cells are
transputted to the progeny and may give rise to inherited
diseases. Mutations thar aries in somatic cells are
important in the genesis of cancers and some congeital
malformations.
Harmful mutations
Benificial mutations
Mutations may be classified
into three catagories:
 GENOME MUTATIONS
- Involve Loss Or Gain Of Whole Chromosomes
(Giving Rise To Monosomy Or Trisomy)
 Chromosome mutations
Result from rearrangement of genetic material and give rise
to visible structural changes in the chromosome.
 Gene mutations
May result in partial or complete deletion of a gene or, more
often, affect a single base. For example, a single nucleotide
base may be substituted by a different base, resulting in a
point mutation.
 Mutations
Mutation:
• Any mistake or change in the DNA sequence

Point mutation:
• Change in
one nitrogen
base in DNA
• Ex: albinism
 Chromosomal Mutation:
• Changes in chromosome structure
1) INVERSION:
occur when a section of DNA breaks away from
a chromosome during the reproductive process and
then reattaches to the chromosome in reversed order
2) TRANSLOCATION
are chromosome mutations in which
chromosome segments, and the genes they contain,
change positions. Translocations can occur within a
chromosome (intrachromosomal) or between
chromosomes (interchromosomal).
3. DELETION
• Loss of a few bases
• Loss of large regions
of a chromosome

4. DUPLICATION
• Duplication of a few bases
• Duplication of large regions of
a chromosome
 Crossing Over

Occurs when
chromosomes exchange
genes.
• 2 chromosomes overlap.
• Some genes cross over
and switch places
 NONDISJUNCTION
Nondisjunction:
• chromosome pair fails to separate
properly during meiosis
Monosomy:
• gamete has 1 less chromosome than
it should
• 45 chromosomes
is the result
• Ex: Turner syndrome
• Missing a sex chromosome
 Trisomy:
• Gamete has 1
more chromosome
than it should
• Result is 47
chromosomes
• Ex: Down’s Syndrome
• Extra #21
chromosome
 Methods of Detection
Chorion villi sampling:
•Take sample of the chorion (membrane surrounding
fetus)
•Chemical tests and Karyotyping performed
•Chromosome analysis or karyotyping is a test that
evaluates the number and structure of a person's
chromosomes in order to detect abnormalities.
Ultrasound:
• Sound waves are used to generate an image of the
unborn child.
• Used to detect abnormalities of limbs, organs, etc.
 Ultrasound
• Many people who hear the term "ultrasound" likely picture a pregnant woman
in her doctor's office getting a sneak peek of the baby growing inside her womb
-- perhaps even finding out whether she should paint the nursery pink or blue.
But while fetal imaging is one of the most common uses of ultrasounds, this
diagnostic tool actually has many applications.

• Ultrasound can be used throughout pregnancy to detect fetal abnormalities.

Ultrasound in the first trimester has been shown to be effective in screening for
aneuploid conditions, such as trisomy 21.
Amniocentesis:
• Fluid surrounding the fetus is drawn out by needle
• Fetal cells are collected and grown in a lab.
• Chromosomes can be then Karyotyped
 Autosomal Disorders
• Inheriting a disease, condition, or trait depends on the type of chromosome affected
(non-sex or sex chromosome). It also depends on whether the trait is dominant or
recessive. A single abnormal gene on one of the first 22 nonsex (autosomal)
chromosomes from either parent can cause an autosomal disorder.

• Down’s Syndrome (Trisomy 21)

• Patau’s Syndrome (Trisomy 13)
• Edward’s Syndrome (Trisomy 18)
 Down’s Syndrome (DS)
• Excess # 21 chromosome
• Prenatal testing can be done
• Result of chromosomal mutation
• 1 in 900 people born with this
• Likelihood of having a child with DS
increases with advancing maternal age
• Symptoms: mental retardation, upward slant
to eyes, small mouth, abnormal ear shape,
decreased muscle tone
• No cure
 EDWARD’S SYNDROME
(also known as Trisomy 18 (T18) or Trisomy E) is a
genetic disorder caused by the presence of all or part of an
extra 18th chromosome. The majority of people with
the syndrome die during the fetal stage; infants who
survive experience serious defects and commonly live for
short periods of time.
 PATAU'S SYNDROME
Patau's syndrome is a serious rare genetic disorder caused by
having an additional copy of chromosome 13 in some or all of the
body's cells. It's also called trisomy 13.
 DELETION DISORDERS

ANGELMAN PRADER-WILLI
SYNDROME SYNDROME
 ANGELMAN SYNDROME

• Angelman syndrome is a complex genetic

disorder that primarily affects the nervous system.
Characteristic features of this condition include:

1.delayed development

2.intellectual disability

3.severe speech impairment and

4.problems with movement and balance (ataxia)

 PRADER-WILLI SYNDROME
• Prader-Willi syndrome (PWS) is a genetic condition that affects
many parts of the body.
• Infants with PWS have severe HYPOTONIA (low muscle
tone), feeding difficulties, and slow growth.
• In later infancy or early childhood, affected children typically
begin to eat excessively and become OBESE. Other signs and

PWS is caused by missing or non-working genes on

chromosome 15. Most cases are not inherited and occur randomly.
Rarely, a genetic change responsible for PWS can be inherited.
Management of PWS generally depends on the affected person's
age and symptoms
 Sex Chromosome Disorders
• Klinefelter’s Syndrome

• Turner’s Syndrome

• Fragile X Syndrome
 Klinefelter’s Syndrome
Klinefelter syndrome (KS) also known as 47,XXY or XXY, is the set
of symptoms that result from two or more X chromosomes in males. The
primary features are infertility and small testicles. Often, symptoms may be
subtle and many people do not realize they are affected.

47, XXY
• 1 in 1000 male live births
• Mild learning difficulties
• Taller than average with long lower limbs
• Show mild enlargement of breasts
• Infertile (absence of sperm)
• Treat with testosterone
 Turner’s Syndrome

Turner syndrome is a chromosomal condition

that affects development in females. The most
common feature of Turner syndrome is short stature,
which becomes evident by about age 5. An early loss
of ovarian function (ovarian hypofunction or
premature ovarian failure) is also very common.
 FRAGILE X SYNDROME
• Fragile X syndrome is a genetic condition that
causes a range of developmental problems
including learning disabilities and cognitive
impairment.

• Usually, males are more severely affected by

this disorder than females. Affected individuals
usually have delayed development of speech and
language by age 2
 SINGLE GENE DISORDERS

Cystic Fibrosis Sickle Cell Anemia

Hemophilia Phenylketonuria
 CYSTIC FIBROSIS (CF)
• Proteins specifically expressed in ductal cells of pancreas. The

enzymes secreted by exocrine glandular cells are transported through

the pancreatic ductal system into the main pancreatic duct that leads to

the duodenum. The ductal epithelium secretes bicarbonate-rich fluid for

regulation of the pH.

• Recessive disorder
• Mutation stops production of protein in lung cells, pancreas
• Thick mucus, bacterial infections in lung
• Most common in Caucasians (1 in 3300)
• Chest percussions, diet supplements
• Shortened life expectancy
 HEMOPHILIA
• Hemophilia is a rare disorder in which your blood

doesn't clot normally because it lacks sufficient blood-

clotting proteins (clotting factors). If you have

hemophilia, you may bleed for a longer time after an

injury than you would if your blood clotted normally.

• Sex-linked
• Failure of blood to clot
• Rare in females
• Injections with clotting factors to stop bleeding episodes
 Sickle Cell Anemia

• Mutation in blood protein

• “sickle” shape to RBC
• Screening tests
• Most common in African-Americans
(1 in 375)
• Pain associated with blocked vessels, causes anemia
(fatigue)
• Common where
mosquito-borne
malaria is present
 PKU
• Mutation disrupts function of enzyme
• Leads to high phenylalanine levels in brain (poisons)
• Mental retardation, epilepsy
• Screening newborns (heel prick)
• 1 in 10,000 Caucasian births
• Extremely rare in African-Americans
• Look normal
• Need low-protein diet,
smelly formulas
 Self Quiz:
Quick Check for Understanding
• 1. Which of the following is an X-linked disorder?
• A. Angelman B. hemophilia c. Down syndrome
• 2. How is PKU tested for?
• A. amniocentesis b. heel prick c. X-ray
• 3. How are CF patients treated?
• A. testosterone injections b. chest percussions
• 4. Turner’s Syndrome is
• A. 45, X b. 46, XX c. 47, XXY
• 5. Patients with Klinefelter’s Syndrome are
• A. all male b. all female c. male or female